Unilateral Aldosterone-producing Adenoma Research Articles

Outcome-Based Decision-Making Algorithm for Treating Patients with Primary Aldosteronism.

BackgroundOptimal management of primary aldosteronism (PA) is crucial due to the increased risk of cardiovascular and cerebrovascular diseases. Adrenal venous sampling (AVS) is the gold standard method for determining subtype but is technically challenging and invasive. Some PA patients do not benefit clinically from surgery. We sought to develop an algorithm to improve decision-making before engaging in AVS and surgery in clinical practice.MethodsWe conducted the ongoing Korean Primary Aldosteronism Study at two tertiary centers. Study A involved PA patients with successful catheterization and a unilateral nodule on computed tomography and aimed to predict unilateral aldosterone-producing adenoma (n=367). Study B involved similar patients who underwent adrenalectomy and aimed to predict postoperative outcome (n=330). In study A, we implemented important feature selection using the least absolute shrinkage and selection operator regression.ResultsWe developed a unilateral PA prediction model using logistic regression analysis: lowest serum potassium level ≤3.4 mEq/L, aldosterone-to-renin ratio ≥150, plasma aldosterone concentration ≥30 ng/mL, and body mass index <25 kg/m2 (area under the curve, 0.819; 95% confidence interval, 0.774 to 0.865; sensitivity, 97.6%; specificity, 25.5%). In study B, we identified female, hypertension duration <5 years, anti-hypertension medication <2.5 daily defined dose, and the absence of coronary artery disease as predictors of clinical success, using stepwise logistic regression models (sensitivity, 94.2%; specificity, 49.3%). We validated our algorithm in the independent validation dataset (n=53).ConclusionWe propose this new outcome-driven diagnostic algorithm, simultaneously considering unilateral aldosterone excess and clinical surgical benefits in PA patients.

Immunohistochemical Analysis of CYP11B2, CYP11B1 and β-catenin Helps Subtyping and Relates With Clinical Characteristics of Unilateral Primary Aldosteronism.

Background: Primary aldosteronism is caused by aldosterone overproduction. While conventional hematoxylin-eosin staining can demonstrate morphological abnormality, it cannot provide any functional histopathological information. We aimed to identify the diagnostic, functional and prognostic value of CYP11B2, CYP11B1, and β-catenin immunostaining in unilateral hyperaldosteronism. Method: A total of 134 patients with unilateral hyperaldosteronism were recruited in our study. The expression of CYP11B2, CYP11B1, and β-catenin was evaluated semiquantitatively on 134 patients’ sections using immunohistochemistry technology and the relationship with clinical data was assessed. Results: Patients were classified into four subtypes based on CYP11B2 staining as below: (1)118 patients with unilateral single aldosterone-producing adenoma (APA), (2)11 with unilateral multiple APA, (3)four with aldosterone-producing cell cluster (APCC), and (4)one with an undefined source. Adjusted CYP11B2 H-score was correlated with serum aldosterone, aldosterone to renin ratio (ARR), and serum potassium. In the abnormal β-catenin staining group, hypertension duration, aldosterone, ARR, cortisol, tumor diameter, tumor area, and CYP11B2 H-score were significantly higher than those of the wild-type group. Serum potassium level was significantly lower in the abnormal β-catenin staining group. Age, gender, BMI, family history of hypertension, adjusted CYP11B2 and CYP11B1 H-scores differed significantly between complete clinical success and incomplete clinical success groups. Age, gender and family history of hypertension were independently associated with complete clinical success based on multivariate logistic regression analysis. Conclusion: CYP11B2 immunostaining could improve the differential diagnosis of unilateral hyperaldosteronism. Adjusted CYP11B2 H-score could be used as a histopathological marker to reflect the severity of unilateral APA. Dysregulation of Wnt/β-catenin signaling and impaired β-catenin degradation may provoke the proliferation and enhance the steroidogenic ability of APA tumor cells, indicating that the Wnt pathway might be a potential, actionable, therapeutic target in the treatment of hyperaldosteronism. Age, sex and family history of hypertension were independent predictors of clinical outcome after adrenalectomy for unilateral hyperaldosteronism.

Diagnosis and treatment of aldosterone-producing adenoma in a young patient: a clinical case

The prevalence of primary hyperaldosteronism (PHA) among individuals with essential arterial hypertension is about 5 to 10%. We present a clinical case of a 32 year old male patient, who despite the full clinical picture of PHA, was managed in primary care setting with the diagnosis of myalgia and treatment-resistant arterial hypertension. The article discusses clinical and laboratory parameters of the patient with the diagnosis of unilateral aldosteroma and the efficacy of its treatment. The generally accepted algorithm of PHA diagnosis with unilateral aldosterone-producing adenoma in young patients does not involve comparative selective blood sampling from adrenal veins. This accelerates the differential diagnosis and facilitates the decision to undertake surgery. This simplified diagnostic algorithm was successfully applied in the patient. Reasonable surgical intervention has led to the recovery of the patient. Awareness of various medical specialties of the up-to-date information on PHA and wide implementation of its screening into clinical practice, first of all, assessment of aldosterone-renin ratio, would allow for detection of the disease as early as possible and prevention of the development of life-threatening cardiovascular complications.

Aldosterone-producing adenoma-harbouring KCNJ5 mutations is associated with lower prevalence of metabolic disorders and abdominal obesity.

Aldosterone overproduction and lipid metabolic disturbances between idiopathic hyperaldosteronism (IHA) and unilateral aldosterone-producing adenoma (APA) have been inconsistently linked in patients with primary aldosteronism. Moreover, KCNJ5 mutations are prevalent among APAs and enhance aldosterone synthesis in adrenal cortex. We aimed to investigate the prevalence of metabolic syndrome (MetS) in each primary aldosteronism subtype and observe the role of KCNJ5 mutations among APAs on the distribution of abdominal adipose tissues quantified using computed tomography (CT), including their changes postadrenalectomy. We retrospectively collected 244 and 177 patients with IHA and APA at baseline. Patients with APA had undergone adrenalectomy, and gene sequencing revealed the absence (n = 75) and presence (n = 102) of KCNJ5 mutations. We also recruited 31 patients with APA who had undergone CT-scan 1-year postadrenalectomy. The patients with APA harbouring KCNJ5 mutations had significantly lower prevalence of MetS and smaller distribution in waist circumference, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) than the other groups. Logistic regression analysis indicated that the VAT area correlated significantly with KCNJ5 mutations among the APAs. Only participants with KCNJ5 mutations had significant increases in triglycerides, cholesterol, SAT, and VAT after 1-year postadrenalectomy. This study is the first to demonstrate that MetS and abdominal obesity were less prevalent in the patients with APA harbouring KCNJ5 mutations compared with the IHA group and the non-KCNJ5-mutated APA group. Increasing prevalence of dyslipidaemia and abdominal obesity was observed in patients with KCNJ5 mutations 1-year postadrenalectomy.

Subtype-specific trends in the clinical picture of primary aldosteronism over a 13-year period.

Primary aldosteronism has two main clinically and biologically distinct subtypes: unilateral aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH). We aimed to evaluate the changes of each subtype's clinical characteristics over a 13-year period. This retrospective study involved time-trend analyses to identify changes in the clinical features of APA and BAH at diagnosis (2006-2018). A nationwide database from 41 Japanese referral centers was searched, which identified 2804 primary aldosteronism patients with complete baseline information and adrenal venous sampling (AVS) data. The proportion of patients with APA decreased from 51% in 2006-2009 to 22% in 2016-2018. Among the 1634 patients with BAH, trend analyses revealed decreases in hypertension duration (median 7--3 years; P < 0.01) and hypokalemia prevalence (18--11%; P < 0.01). However, among the 952 patients with APA, there were no significant changes in hypertension duration (median 8 years) and hypokalemia prevalence (overall 70%). Furthermore, the APA group had a trend towards increased use of multiple hypertensive drugs at diagnosis (30--43%; P < 0.01). When subtypes were reclassified according to the precosyntropin stimulation AVS data, APA patients tended to be diagnosed earlier and at milder forms, consistent with the trend in overall primary aldosteronism patients. During 2006-2018, we identified marked subtype-specific trends in the clinical findings at the diagnosis of primary aldosteronism. Our results suggested that the emphasis on the implementing cosyntropin stimulation during AVS might lead to under-identification of APA, especially in patients with mild or early cases.

Partial versus total adrenalectomy for the treatment of unilateral aldosterone-producing adenoma: a systematic review and meta-analysis.

Adrenalectomy is the first line of treatment in unilateral aldosterone-producing adenoma. Whether adrenalectomy should be performed using a cortex-sparing technique (partial adrenalectomy) or total adrenalectomy remains debatable. Therefore, this meta-analysis aims to evaluate the safety and effectiveness of partial adrenalectomy (PA) to total adrenalectomy (TA) by comparing perioperative and functional outcomes. A systematic search was performed across Pubmed, Embase, Web of Science, Cochrane Library database for RCTs and non-RCTs comparing PA and TA on unilateral aldosterone-producing adenoma. The main outcomes analyzed were the perioperative and postoperative effectiveness. In addition, weighted mean difference (WMD) or odds ratio (OR) with 95% confidence intervals of continuous and dichotomous variables are presented. Two RCTs and 5 non-RCTs trials, including 834 patients were identified and included in the meta-analysis. PA was associated with statistically significant shorter hospital stay (WMD - 0.51days, 95% CI - 0.87, - 0.14; p = 0.007), shorter operative time (WMD - 15.54min, 95% CI - 25.12, - 5.97; p = 0.001) and lower overall complications (OR 0.52, 95% CI 0.32, 0.85; p = 0.009) compared to TA. There was no statistical significance in postoperative effectiveness, including postoperative blood pressure, potassium, hypokalemia, ARR and renin between TA and PA. PA seems to have advantages over TA. The surgical outcomes were comparable in TA and PA. The hospital stay, operative time and overall complications may be reduced. When technically feasible, PA might be considered as a better treatment for unilateral aldosterone-producing adenoma.

HIGH LEVEL OF PLASMA ALDOSTERONE AFTER SALINE INFUSION TEST IN COMBINATION WITH FINDING OF ADRENAL NODE ON CT SCAN CAN PREDICT ALDOSTERONE-PRODUCING ADENOMA MORE PRECISE THAN FINDING OF NODE ALONE

Objective: Idiopathic aldosteronism due to bilateral hyperplasia and unilateral aldosterone-producing adenoma of adrenal gland are two main forms of primary aldosteronism. The discrimination between unilateral and bilateral aldosterone overproduction is crucial for an appropriate management of patients with primary aldosteronism. This study tests the reliability of plasma aldosterone after the postural stimulation test and after the saline infusion test in combination with finding of adrenal node on CT scan for the identification of these two common forms of primary aldosteronism. Methods: One hundred and fifty patients with laboratory diagnosis of primary aldosteronism (96 patients with confirmed diagnosis of aldosterone producing adenoma and 54 patients with idiopathic aldosteronism were enrolled into the study. All of patients underwent CT scan, the postural stimulation test, the saline infusion test and adrenal venous sampling. Design and method: Plasma aldosterone concentration in the supine or in the standing position and after the saline infusion were higher in patients with aldosterone-producing adenoma than in those with idiopathic aldosteronism (P &lt; 0.001; P &lt; 0.01 and P &lt; 0.001, respectively). The largest area under the curve = 0.83 (for a cut-off of 165 ng/l) suggesting the diagnosis of unilateral aldosterone overproduction was found for finding of adrenal node on CT scan in combination with plasma aldosterone concentration after the saline infusion test with a sensitivity of 83%, specificity of 61%, positive-predictive value of 79% and negative-predictive value of 67%. Results: The study found that the value of plasma aldosterone concentration ?165 ng/l after the saline infusion test in combination with finding of node on CT scan can predict aldosterone-producing adenoma more precise than finding of node alone, nevertheless, results of adrenal venous sampling remain to be crucial in the identification of two common forms of primary aldosteronism. The study found that the value of plasma aldosterone concentration ?165 ng/l after the saline infusion test in combination with finding of node on CT scan can predict aldosterone-producing adenoma more precise than finding of node alone, nevertheless, results of adrenal venous sampling remain to be crucial in the identification of two common forms of primary aldosteronism.

Thirty-six-month results of laparoscopic-based renal denervation plus unilateral laparoscopic adrenalectomy for the treatment of patients with resistant hypertension caused by unilateral aldosterone-producing adenoma.

The aim of this study was to explore the long‐term clinical results of Renal denervation (RDN) from the adventitia of the renal artery plus unilateral laparoscopic adrenalectomy to treat patients with resistant hypertension caused by unilateral aldosterone‐producing adenoma (APA). Sixty patients with resistant hypertension caused by APA who were treated at Henan Provincial People's Hospital from December 2016 to March 2018 were selected and randomly assigned to undergo RDN from the adventitia of the renal artery plus adrenalectomy (RDN group, n = 30) or adrenalectomy alone (control group, n = 30). Office blood pressure (BP), antihypertensive medication usage and other laboratory characteristics were followed every 6 months through 36 months. Follow‐up data were available at 36 months for 23 of 30 subjects in the RDN group and for 21 of 30 subjects who were in the control group. At 36 months postprocedure, the reduction in the RDN group was 42.2 ± 21.6 mmHg and that in the control group was 29.8 ± 13.5 mmHg (p = .029 between the groups). During the follow‐up to 36 months postprocedure, no patients in either the RDN group or the control group died due to surgical complications, and the RDN group had no procedural complications, including renal artery dissection, perforation, and renal artery stenosis. There was no change in the mean eGFR of the two groups, and no serious adverse events were reported. In conclusion, RDN from the adventitia of the renal artery plus unilateral laparoscopic adrenalectomy resulted in sustained lowering of BP at 3 years in a selected population of subjects with resistant hypertension caused by unilateral APA without serious safety concerns.

Hypertension Editors' Picks: Hyperaldosteronism.

Hypertension Editors' Picks: Hyperaldosteronism.

Diverse pathological lesions of primary aldosteronism and their clinical significance

Primary aldosteronism (PA) is mainly clinically classified as unilateral aldosterone-producing adenoma (APA) or bilateral idiopathic hyperaldosteronism. Immunohistochemistry for aldosterone synthase reveals a diverse PA pathology, including pathological APA and aldosterone-producing cell clusters. The relationship between PA pathology and adrenalectomy outcomes was examined herein. Data from 219 unilaterally adrenalectomized PA cases were analyzed. Pathological analyses revealed diverse putative aldosterone-producing lesions. Postoperative biochemical outcomes in 114 cases (test cohort) were classified as complete success (n = 85), partial success (n = 19), and absent success (n = 10). Outcomes in the large and small PA lesion groups, rather than between PA lesion types, were compared at five threshold values for PA lesion sizes (2–6 mm with 1-mm increments) to streamline the results. The proportion of complete success was significantly higher in the large PA lesion group than in the small PA lesion group at the 5-mm threshold only. The proportion of absent success was significantly higher in the small PA lesion group than in the large PA lesion group at all thresholds. Univariate and multivariate analyses of the test cohort identified serum K as an independent predictive factor for the small PA lesion group, which was confirmed in the 105-case validation cohort. Chi-squared automatic interaction detector analysis revealed that the best threshold of serum K for predicting large PA lesions was 2.82 mEq/L. These results will be beneficial for treating PA in clinical settings because patients with low serum K levels and apparent adrenal masses on CT may be subjected to adrenalectomy even if the adrenal venous sampling test is unavailable.

Aldosterone-induced cardiac damage in primary aldosteronism depends on its subtypes.

ObjectivesThis study compared cardiac function, morphology, and tissue characteristics between two common subtypes of primary aldosteronism (PA) using a 3T MR scanner.DesignA retrospective, single-center, observational study.MethodsWe retrospectively reviewed 143 consecutive patients with PA, who underwent both adrenal venous sampling and cardiac magnetic resonance. We acquired cine, late gadolinium enhancement, and pre- and postcontrast myocardial T1-mapping images.ResultsPA was diagnosed as unilateral aldosterone-producing adenoma (APA) in 70 patients and bilateral hyperaldosteronism (BHA) in 73. The APA group showed significantly higher plasma aldosterone concentration (PAC) and aldosterone to renin rate (ARR) than the BHA group. After controlling for age, sex, antihypertensive drugs, systolic and diastolic blood pressure, and disease duration, the parameters independently associated with APA were: left ventricular end-diastolic volume index (EDVI: adjusted odds ratio (aOR) = 1.06 (95% CI: 1.030–1.096), P < 0.01), end-systolic volume index (ESVI: 1.06 (1.017–1.113), P < 0.01), stroke index (SI: 1.07 (1.020–1.121), P < 0.01), cardiac index (CI: 1.001 (1.000–1.001), P < 0.01), and native T1 (1.01 (1.000–1.019), P = 0.038). Weak positive correlations were found between PAC and EDVI (R = 0.28, P < 0.01), ESVI (0.26, P < 0.01), and SI (0.18, P = 0.03); and between ARR and EDVI (0.25, P < 0.01), ESVI (0.24, P < 0.01), and native T1 (0.17, P = 0.047).ConclusionsAPA is associated with greater LV volumetric parameters and higher native T1 values, suggesting a higher risk of volume overload and myocardial damage.

Aldosterone is Aberrantly Regulated by Various Stimuli in a High Proportion of Patients with Primary Aldosteronism

In primary aldosteronism (PA), aldosterone secretion is relatively independent of the renin-angiotensin system, but can be regulated by several other stimuli. To evaluate aldosterone response to several stimuli in a series of patients with PA secondary either to bilateral adrenal hyperplasia (BAH) or unilateral aldosterone-producing adenoma (APA). Prospective cohort study conducted in a university teaching hospital research center. Forty-three patients with confirmed PA and subtyped by adrenal vein sampling (n = 39) were studied, including 11 with BAH, 28 with APA, and 4 with undefined etiology. We also studied 4 other patients with aldosterone and cortisol cosecretion. We systematically explored aberrant regulation of aldosterone using an in vivo protocol that included the following stimulation tests performed over 3 days under dexamethasone suppression: upright posture, mixed meal, adrenocorticotropin (ACTH) 1-24, gonadotropin-releasing hormone (GnRH), vasopressin, and serotonin R4 agonist. Positive response was defined as >50% renin or ACTH-independent increase in plasma aldosterone/cortisol concentration following the various stimulation tests. Renin-independent aldosterone secretion increased in response to several aberrant stimuli (upright posture, GnRH) in up to 83% of patients with APA or BAH in whom ACTH 1-24 and HT4R agonists also produced aldosterone oversecretion in all patients. The mean significant aberrant responses per patient was similar in BAH (4.6) and in APA (4.0). Aldosterone secretion in PA is relatively autonomous from the renin-angiotensin system, but is highly regulated by several other stimuli, which contributes to the large variability of aldosterone levels in PA patients.

Clinical outcomes of laparoscopic-based renal denervation plus adrenalectomy vs adrenalectomy alone for treating resistant hypertension caused by unilateral aldosterone-producing adenoma.

Previous studies describing renal denervation (RDN) from the intima of the renal artery for the treatment of resistant hypertension have reported variable efficacies, and RDN triggers renal intimal injury and atherosclerosis. This study aimed to evaluate the efficacy and safety of RDN from the adventitia of renal artery plus unilateral laparoscopic adrenalectomy to treat patients with resistant hypertension caused by unilateral aldosterone-producing adenoma (APA). A total of 60 consecutive patients with resistant hypertension caused by unilateral APA were enrolled in this study. Patients were randomly assigned to undergo RDN from the adventitia of the renal artery plus adrenalectomy (RDN group, n=30) or adrenalectomy alone (control group, n=30) and were followed up for 12months. The primary efficacy end point was the change in 24-hours mean ambulatory systolic blood pressure (SBP) from baseline to 12months. At the 12-month follow-up, the mean reduction of 24-hours average SBP and office SBP in the RDN group was 20.7±15.2 and 37.1±26.0mmHg, respectively, which was significantly higher than the mean reduction of 24-hours average SBP (11.9±11.1mmHg, P=.017) and the office SBP (25.9±16.8mmHg, P=.035) in the control group. Serum potassium levels returned to normal 12months post-procedure. Patients in the RDN group had higher proportion of cured clinical and biochemical outcomes than those in the control group (35.7% vs 17.9% in clinical outcome; 96.4% vs 89.3% in biochemical outcome, respectively). There were no procedural-, device-, or treatment-related safety events during the 12-month follow-up period between the groups. In conclusion, RDN from the adventitia of the renal artery plus unilateral laparoscopic adrenalectomy is more effective than adrenalectomy alone for treating resistant hypertension caused by unilateral APA.

Precise Mapping of Intra-Adrenal Aldosterone Activities Provides a Novel Surgical Strategy for Primary Aldosteronism.

Segmental selective adrenal venous sampling (sAVS) elucidates an intraadrenal aldosterone activity map (IAMap), which allows us to design a novel surgical treatment strategy for patients with primary aldosteronism. We evaluated the usefulness of sAVS by analyzing 278 patients with whom we had prospectively used IAMap using the criteria of sAVS for surgical indication between 2009 and 2015. We evaluated its diagnostic accuracy using pathological and postsurgical biochemical and clinical outcomes. One hundred twenty and 158 patients were diagnosed with unilateral and bilateral disease, respectively, through sAVS. The concordance of lateralization diagnosis with computed tomography imaging was 66.6%. Among the unilateral patients, we performed partial adrenalectomy in 68 patients whose IAMap showed focal aldosterone hypersecretion from computed tomography-detectable tumor in the affected adrenal gland. All of them achieved complete biochemical success 1 year after surgery. Furthermore, 25 of 158 bilateral disease patients underwent surgical resection because they were preoperatively diagnosed as bilateral aldosterone-producing adenomas by IAMap. These cases showed complete or partial biochemical success (28.0% and 72.0%, respectively); 36.0% showed complete clinical success. Pathological studies demonstrated that all 145 resected specimens possessed aldosterone-producing adenoma or multiple nodules (132 and 13 cases, respectively), and none showed diffuse hyperplasia. IAMap accurately diagnosed both bilateral and unilateral aldosterone-producing adenomas and diffuse hyperplasia before surgery. sAVS allows a novel surgical strategy for selected PA patients with favorable outcomes.

MON-210 Role of Female Gender and Subcutaneous Fat in the Positive Association of Obesity with Idiopathic Hyperaldosteronism

Context: Primary aldosteronism (PA) is the most frequent cause of secondary hypertension. The relationship between PA and various metabolic disorders including obesity, diabetes mellitus and dyslipidemia has been reported. On the other hand, PA consists of two main subtypes: unilateral aldosterone-producing adenoma (APA) and the bilateral idiopathic hyperaldosteronism (IHA), which have different etiologies. Recently, it was reported that the prevalence of obesity was higher in patients with IHA than those with APA, suggesting that there is a link between obesity and the etiology of IHA (Ohno Y et al. J Clin Endocrinol Metab 2018). Furthermore, it has also been reported that female patients with PA are more likely to have IHA than male patients. Objective: Our objective was to clarify the pathological role of female gender in the positive association of obesity with IHA. Because of the difference of body fat distribution between men and women, we also investigate the contribution of visceral and subcutaneous fats in the pathogenesis of IHA. Design: This retrospective observational study comprised 117 PA patients (IHA: n = 73, APA: n = 44) diagnosed by adrenal venous sampling between January 2006 and July 2019 at Jichi Medical University Hospital. We compared prevalence of obesity and metabolic parameters including visceral and subcutaneous fat areas measured by computed tomography between patients with IHA and APA by gender. We also compared visceral and subcutaneous fat areas between patients with IHA and APA by the presence of obesity, BMI ≥25 kg/m2 (the diagnosis criteria by Japan Society for the Study of Obesity). Results: In consistent with previous reports, BMI was significantly higher in patients with IHA than those with APA. However, in male patients, no difference of BMI between IHA and APA was observed. By contrast, in female patients, not only BMI but also both visceral and subcutaneous fat areas were significantly higher in IHA than in APA. Next, we investigated the contribution of visceral and subcutaneous fats in the positive association of obesity with IHA in female patients. Subcutaneous fat area but not visceral fat area was significantly higher in female obese patients with IHA. By contrast, visceral fat area but not subcutaneous fat area was significantly higher in female non-obese patients with IHA. Conclusions: These results suggest that obesity, especially subcutaneous fat accumulation, contributes to the pathogenesis of IHA in female patients.

PD31-02 WHAT TIMING IS APPROPRIATE FOR A BIOCHEMICAL EVALUATION AFTER LAPAROSCOPIC ADRENALECTOMY FOR UNILATERAL ALDOSTERONE-PRODUCING ADENOMA?

INTRODUCTION AND OBJECTIVE: The over-secretion of plasma aldosterone by unilateral aldosterone-producing adenoma (APA) can be cured by adrenalectomy. However, the time needed for the endocrine environment to normalize remains unclear. The aim of this study is to clarify adequate timing for a biochemical evaluation in unilateral APA patients after adrenalectomy. METHODS: A total of 166 unilateral APA patients were retrospectively reviewed. We evaluated renin-angiotensin axis agents: the plasma aldosterone concentration (PAC) (pg/ml), active renin concentration (ARC) (pg/ml) and aldosterone-renin ratio (ARR: PAC/ARC), serum potassium concentration, and estimated glomerular filtration rate (eGFR) at 1, 3, and 6 post operation months (POM). By applying the Primary Aldosteronism Surgical Outcome criteria, which is based with ARR, PAC and serum potassium levels, biochemical outcomes were also evaluated. RESULTS: PAC was significantly lower at 1POM than at pre-surgery (pre-surgery; 407.2, 1 POM; 90.0 pg/mL, p<0.001) (Fig. A). ARC did not increase from baseline at 1POM, but significantly increased at 3POM (pre-surgery; 4.43, 1POM; 4.87, 3POM; 11.3 pg/mL, p<0.001) (Fig. B). The patients who didn’t achieve the ARC normalization at 1POM had lower pre-surgery ARC (p<0.001) and higher pre-surgery 24-hour urinary aldosterone excretion (p=0.042). Although ARC did not significantly increase at 1POM, ARR significantly decreased at 1POM (pre-surgery; 146.9, 1 POM; 26.3, p<0.001) (Fig. C). Among the 34 patients who had hypokalemia pre-surgery, it was resolved in 28 (82%) at 1POM and in all (100%) at 3POM (Fig. D). The biochemical outcomes at 1POM were 131 (79%) complete, 20 (12%) partial, and 15 (9%) absent successes, while at 3POM, 147 (89%) were complete, 9 (5%) partial, and 10 (6%) absent. Twenty-three (14%) patients were changed biochemical outcomes between 1 and 3POM, whereas only 5 (3%) changed between 3 and 6POM. CONCLUSIONS: The appropriate timing for a biochemical evaluation of unilateral APA patients treated with laparoscopic adrenalectomy appears to be 3 months or more after surgery.Source of Funding: None

Imaging CXCR4 expression in patients with suspected primary hyperaldosteronism

It is challenging to differentiate unilateral aldosterone-producing adenoma (APA) from bilateral idiopathic adrenal hyperplasia (IAH) and nonfunctional adrenal adenoma (NFA) in primary aldosteronism (PA). In a first primarily ex vivo study detection, CXC chemokine receptor type 4 (CXCR4) expression has been shown to be a valuable tool for the detection of APA. In this study, we aimed to clinically evaluate CXCR4 imaging with 68Ga-pentixafor PET/CT for detecting APA. We prospectively recruited 36 patients with clinical suspicion of PA. All patients underwent 68Ga-pentixafor PET/CT. Positive lesions were defined based on higher tracer uptake in adrenal nodular(s) shown on CT than the normal adrenal. These lesions were referred for adrenalectomy subsequently. All patients received clinical follow-up. Semi-quantitative analysis using maximum standardized uptake value (SUVmax), lesion-to-liver ratio (LLR), and lesion-to-contralateral ratio (LCR) has also been performed. PET/CT results were correlated with clinical presentation and follow-up. Thirty-nine adrenal lesions in 36 patients were found; 25 APA, 4 IAH, and 10 NFA according to histopathology and clinical assessment. Sensitivity, specificity, and accuracy of 68Ga-pentixafor PET/CT in distinguishing APA by visualization were 100%, 78.6%, and 92.3% respectively. The SUVmax of APA (21.34 ± 9.41, n = 25) was significantly higher than that of non-APA lesions (6.29 ± 2.10, n = 14, P < 0.0001). An optimal threshold of SUVmax = 11.18 was determined for predicting APA with a sensitivity of 88.0%, specificity of 100%, and an accuracy of 92.3%. A cutoff value for LCR of 2.12 yielded a sensitivity of 100% and a specificity of 92.9%, whereas a cutoff value for LLR of 2.36 reached at both 100% of sensitivity and specificity. All patients with (removed) positive lesions benefited from surgery. 68Ga-Pentixafor PET/CT may be used to non-invasively detect APA in PA patients.

MicroRNAs and Adrenocortical Tumors: Where do we Stand on Primary Aldosteronism?

MicroRNAs, the endogenous mediators of RNA interference, interact with the renin-angiotensin-aldosterone system, regulate aldosterone secretion and aldosterone effects. Some novel data show that the expression of some microRNAs is altered in primary aldosteronism, and some of these appear to have pathogenic relevance, as well. Differences in the circulating microRNA expression profiles between the two major forms of primary aldosteronism, unilateral aldosterone-producing adenoma and bilateral adrenal hyperplasia have also been shown. Here, we present a brief synopsis of these findings focusing on the potential relevance of microRNA in primary aldosteronism.

Lipoprotein insulin resistance score and branched-chain amino acids increase after adrenalectomy for unilateral aldosterone-producing adenoma: a preliminary study

Background and aimsPrimary aldosteronism (PA) due to unilateral aldosterone-producing adenoma (APA) is preferentially treated by unilateral adrenalectomy (ADX), but little is known about the changes in lipid and glucose metabolism that may occur after ADX.MethodsWe studied 19 non-diabetic patients who did not use lipid-lowering drugs with PA due to APA before and 6 months after unilateral ADX. Fasting plasma lipids, lipoprotein subfractions, branched-chain amino acids (BCAA), and GlycA, a pro-inflammatory glycoprotein biomarker, were measured by nuclear magnetic resonance (NMR) spectroscopy. The Lipoprotein Insulin Resistance (LP-IR) score, which is based on six lipoprotein variables, was calculated.ResultsIn all patients, hyperaldosteronism was resolved after ADX. Body mass index and fasting plasma glucose were unchanged, but HbA1c increased (p = 0.002). Plasma triglycerides, large triglyceride-rich lipoprotein (TRL) cholesterol, and large TRL particles were increased (p < 0.01), resulting in an increase in TRL size (p = 0.027). High-density lipoprotein size was decreased (p = 0.015). LP-IR scores (p = 0.001) and total BCAA (p = 0.017) were increased, but GlycA remained unaltered.ConclusionsBased on increases in LP-IR scores and BCAA, which each have been shown to predict new onset type 2 diabetes mellitus independent of conventional risk factors in the general population, this preliminary study suggests that diabetes risk is not improved but may even be increased after ADX for APA despite remission of PA.

Appropriate timing for a biochemical evaluation after adrenalectomy for unilateral aldosterone-producing adenoma.

The oversecretion of plasma aldosterone by unilateral aldosterone-producing adenoma (APA) can be cured by adrenalectomy. However, the time needed for the endocrine environment to normalize remains unclear. To clarify adequate timing for a biochemical evaluation in unilateral APA patients after adrenalectomy. A total of 166 unilateral APA patients were retrospectively reviewed. We evaluated the plasma aldosterone concentration (PAC) (pg/mL), active renin concentration (ARC) (pg/mL), aldosterone-renin ratio (ARR; PAC/ARC), serum potassium concentration and estimated glomerular filtration rate (eGFR) at 1, 3 and 6 postoperation months (POM). PAC was significantly lower at 1POM than at presurgery (presurgery; 407.2, 1 POM; 90.0pg/mL, P<.001). ARC did not increase from baseline at 1POM, but significantly increased at 3POM (presurgery; 4.43, 1POM; 4.87, 3POM; 11.3pg/mL, P<.001). ARR significantly decreased at 1POM (presurgery; 146.9, 1 POM; 26.3, P<.001) although ARC did not increase at 1POM. Among the 34 patients who had hypokalaemia presurgery, it was resolved in 28 (82%) at 1POM and in all (100%) at 3POM. The biochemical outcomes at 1POM were 131 (79%) complete, 20 (12%) partial and 15 (9%) absent successes, while at 3POM, 147 (89%) were complete, 9 (5%) partial and 10 (6%) absent. Twenty-three (14%) patients were reclassified into different biochemical outcomes between 1 and 3POM, whereas only 5 (3%) changed between 3 and 6POM. The appropriate timing for a biochemical evaluation of unilateral APA patients treated with laparoscopic adrenalectomy appears to be 3months or more after surgery.